DESCRIPTION: Quantitative, domain specific assays for inhibitors to factor VIII will be developed. These assays will be used in a comprehensive analysis of inhibitors in hemophilia A patients and patients with autoantibodies to factor VIII. The immunologic response to factor VIII infusions in previously untreated patients will be characterized. The T cell response in inhibitor development will be characterized by the generation of factor VIII-specific T cell lines from peripheral blood mononuclear cells from inhibitor patients. The factor VIII sequences that react with these T cells will be determined. A murine model of hemophilia will be used to study the interaction of factor VIII specific peptides, T cell receptors, and the MHC II complex.